@article{cfb22007c83b4ed8a7faf891c10ba0f9,
title = "Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC",
abstract = "Background/Aims: We have investigated the role of natural killer (NK) cells in hepatic fibrogenesis. Mouse NK cells express both inhibitory/activating-killing-immunoglobulin-related-receptors (iKIR/aKIR) specific for Class-I-molecules. Methods: Hepatic fibrosis induced by carbon-tetrachloride (CCl4) was compared between wild-type (WT) male-BALBc; combined-immunodeficiency (SCID, lacking B/T-cells); and SCID-BEIGE-mice (lacking B/T/NK cells), and naive mice. Results: Hepatic fibrosis significantly increased in all CCl4-treated groups. SCID-BEIGE mice had more fibrosis than SCID-mice (P < 0.0001) as assessed by morphometry of sirius-red stained tissue sections. Following fibrosis, hepatic NK cells significantly decreased, the aKIR:iKIR-ratio significantly increased while Class-I expression on HSC decreased (P < 0.001). Both freshly isolated and in situ HSC displayed a significant increase in cellular apoptosis following fibrosis induction. Confocal microscopy demonstrated the direct adhesion of NK cells to HSC in mouse liver sections and in vitro human NK/HSC co-culture. In human HSC there was decreased Class-I expression and increased apoptosis as well, which was further increased following blocking of either HSC-related Class-I or NK-related killer inhibitory receptors. Apoptosis was inhibited by pre-incubation of NK cells with the granzyme inhibitor 3,4-dichloroisocoumarin. Conclusions: During liver injury, NK cells have an anti-fibrotic activity at least in part through stimulation of HSC killing.",
keywords = "Hepatic fibrosis, Hepatic stellate cells, KIR, Lymphocytes, NK cells, SCID",
author = "Alaa Melhem and Nidal Muhanna and Amal Bishara and Alvarez, {Carlos E.} and Yaron Ilan and Taiser Bishara and Amjad Horani and Mithal Nassar and Friedman, {Scott L.} and Rifaat Safadi",
note = "Funding Information: This work was supported by grants from {\textquoteleft}Return to Hadassah,{\textquoteright} {\textquoteleft}Compensatory{\textquoteright} and {\textquoteleft}Salzburg{\textquoteright} Awards, the Israel Science Foundation (grant No.8033601, 8033603, 8033604 to RS), The Feld Fibrosis Foundation at Mount Sinai, and the National Institutes of Health (DK56621 to SLF). ",
year = "2006",
month = jul,
doi = "10.1016/j.jhep.2005.12.025",
language = "אנגלית",
volume = "45",
pages = "60--71",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
number = "1",
}
